The insulin receptor is a heterotetrameric membrane bound glycoprotein composed of two predominantly extracellular alpha subunits that bind insulin and two beta subunits that span the membrane and are capable of demonstrating autophosphorylation as well as containing tyrosine kinase activity in their cytoplasmic domain. Brain insulin receptors are smaller than non-neural insulin receptors, as seen on sodium dodecyl sulphate polyacrylamide gel electrophoresis. This difference in molecular weight is mainly due to differences in glycosylation as demonstrated by insensitivity of brain insulin receptors to neuraminidase digestion. Phylogenetic and ontogenetic studies demonstrated that the difference in brain insulin receptors is evolutionarily and developmentally well conserved. Despite these structural differences, brain insulin receptors, like their non-neural counterparts, are capable of undergoing insulin-induced autophosphorylation of the beta subunit as well as insulin-stimulated phosphorylation of tyrosine specific artificial substrates. Thus insulin receptors on nervous tissue are capable of responding normally to insulin.